title: Leukotriene-induced contraction is mediated by cysteinyl leukotriene receptor CysLT1 in guinea pig fundus but by CysLT1 and CysLT2 in antrum.
abstract: OBJECTIVE
  Leukotriene D(4) (LTD(4)) causes contraction of the stomach through unclear receptors. The aim of the present study is to characterize the cysteinyl leukotriene receptor (CysLT) mediating leukotriene-induced muscle contraction in the stomach.
  
  
  METHODS
  We measured contraction of gastric muscle strips isolated from the guinea pig fundus and antrum caused by cysteinyl leukotrienes, including LTC(4), LTD(4) and LTE(4), as well as the dihydroxy leukotriene LTB(4) in vitro.
  
  
  RESULTS
  In both fundic and antral muscle strips, LTC(4) and LTD(4) caused marked whereas LTE(4) caused moderate, concentration-dependent contractions. In contrast, LTB(4) caused only small contraction. The relative potencies for cysteinyl leukotrienes to cause contraction in both fundus and antrum were LTC(4)=LTD(4)>LTE(4). The LTD(4)-induced contraction was not affected by tetrodotoxin or atropine, suggesting that the action is not neurally mediated. The LTD(4)-induced contraction in the fundus was almost abolished by the CysLT(1) selective antagonist montelukast. In contrast, the LTD(4)-induced contraction in the antrum was only partially inhibited by montelukast or the dual CysLT(1) and CysLT(2) antagonist BAY u9773. This antral contraction was almost abolished by the combination of montelukast and BAY u9773, indicating enhancement of inhibition.
  
  
  CONCLUSIONS
  The results of the present study demonstrate that cysteinyl leukotrienes LTC(4), LTD(4) and LTE(4) cause moderate to marked whereas the dihydroxy leukotriene LTB(4) causes small muscle contraction in the stomach in vitro. The leukotriene-induced contraction is mediated by CysLT(1) in fundus but by CysLT(1) and CysLT(2) in antrum.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, and School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan. shihchehuang@hotmail.com
authors.forename: Shih-Che
authors.initials: SC
authors.lastname: Huang
mesh_terms: D000085:Acetates / Q000494:pharmacology; D000818:Animals; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D005748:Gastric Fundus / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D017997:Leukotriene C4 / Q000494:pharmacology; D017998:Leukotriene D4 / Q000494:pharmacology*; D017999:Leukotriene E4 / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D011706:Pyloric Antrum / Q000187:drug effects* / Q000502:physiology; D011804:Quinolines / Q000494:pharmacology; D018077:Receptors, Leukotriene / Q000187:drug effects / Q000502:physiology*; D013189:SRS-A / Q000031:analogs & derivatives / Q000494:pharmacology; D013440:Sulfides
chemical_list: D000085:Acetates; C071435:BAY u9773; D003521:Cyclopropanes; D011804:Quinolines; D018077:Receptors, Leukotriene; D013189:SRS-A; D013440:Sulfides; D017997:Leukotriene C4; D017998:Leukotriene D4; D017999:Leukotriene E4; C083169:leukotriene D4 receptor; C093875:montelukast